Reactive Arthritis

Overview

Reactive arthritis is a seronegative spondyloarthropathy that occurs after a genitourinary or gastrointestinal infection, typically presenting as an asymmetric oligoarthritis, often with associated conjunctivitis and urethritis (formerly Reiter’s syndrome). It most commonly affects young adults aged 20–40 and shows a strong association with HLA-B27. Incidence is estimated at 30–40 per 100,000, with higher rates in HLA-B27–positive individuals following infection.

Anatomy and Physiology

Aetiology and Risk Factors

• Infectious triggers (precede arthritis by ~1–4 weeks):
  • GU: Chlamydia trachomatis
  • GI: Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile
• HLA-B27 positivity (increases risk and severity)
• Young age (20–40 years)
• Male sex (especially with genitourinary infections)
• Immunogenetic susceptibility

Pathophysiology

• Initial GI or GU infection triggers immune activation
• Bacterial antigens persist in synovium or gut mucosa (molecular mimicry)
• Dysregulated immune response involving CD8+ T cells, cytokines (IL-17, TNF-α)
• Results in sterile synovitis, enthesitis, and extra-articular inflammation

Clinical Manifestations

• Arthritis
  • Asymmetric oligoarthritis (knees, ankles, MTPs)
  • Dactylitis (“sausage digit”)
  • Heel pain (enthesitis)
  • Lower back pain (sacroilitis)
• Ocular Conjunctivitis (mild), anterior uveitis (painful)
• Urogenital: Urethritis, cervicitis, prostatitis
• Mucocutaneous:
  • Oral ulcers
  • Circinate balanitis
  • Keratoderma blennorrhagicum (psoriasiform rash)
• Systemic symptoms: Fever, malaise, weight loss

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Diagnosis

No dedicated ReA classification criteria. Often diagnosed clinically based on:
– Acute oligoarthritis
– Preceding GI/GU infection
– Absence of live pathogen in joint fluid

Investigations

• Stool or urine PCR/culture: to identify trigger organism
• HLA-B27 testing: positive in ~50–80% of cases
• CRP/ESR: often elevated
• Joint aspiration: to rule out septic arthritis (crystals, WBCs, culture)
• X-ray/MRI: May show periostitis, enthesitis, sacroiliitis in chronic cases

Differential Diagnoses:

Treatment

Acute management

• NSAIDs: first-line for arthritis and enthesitis
• Intra-articular corticosteroids: for persistent monoarthritis
• Short course oral corticosteroids: if polyarthritis or systemic symptoms
• Antibiotics: only if infection is still active (e.g. Chlamydia)

Chronic/refractory disease

• DMARDs: sulfasalazine or methotrexate for persistent arthritis
• Anti-TNF agents: for chronic or axial disease unresponsive to DMARDs

Supportive: Physiotherapy, sexual health counselling, patient education

Complications and Prognosis

• Most cases resolve within 3–6 months
• ~30% may have chronic arthritis or relapsing flares
• Chronic ReA more likely with HLA-B27, severe initial disease, or poor treatment response
• Extra-articular complications (e.g. uveitis, enthesitis, sacroiliitis) may persist
• Rare: aortic valve involvement, amyloidosis

Poor Prognostic Factors

• HLA-B27 positivity
• Chronic sacroiliitis
• High inflammatory markers
• Recurrent infection

References

1. Hannu T. Reactive arthritis. Best Pract Res Clin Rheumatol. 2011;25(3):347–357.
2. Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: pathogenetic and clinical considerations. Clin Microbiol Rev. 2004;17(2):348–369.
3. Braun J, Kingsley G, van der Heijde D, Sieper J. On the difficulties of establishing a consensus definition of reactive arthritis. J Rheumatol. 2000;27(10):2185–2187.
4. Carter JD, Hudson AP. Reactive arthritis: clinical aspects and medical management. Rheum Dis Clin North Am. 2009;35(1):21–44.